title: Branched chain amino acids are associated with muscle mass in functionally limited older adults.
abstract: BACKGROUND
  Metabolic profiling may provide insight into biologic mechanisms related to the maintenance of muscle and fat-free mass in functionally limited older adults. The objectives of the study were to characterize the association between thigh muscle cross-sectional area (CSA) and the fat-free mass index (FFMI; total lean mass/height(2)) with the serum metabolite profile, to further identify significant metabolites as associated with markers of insulin resistance or inflammation, and to develop a metabolite predictor set representative of muscle CSA and the FFMI in functionally limited older adults.
  
  
  METHODS
  Multivariable-adjusted linear regression was used on mass spectrometry-based metabolomic data to determine significant associations between serum metabolites with muscle CSA and the FFMI in 73 functionally limited (Short Physical Performance Battery ≤ 10) older adults (age range: 70-85 years). Significant metabolites were further examined for associations with markers of insulin resistance (homeostasis model assessment of insulin resistance) or inflammation (tumor necrosis factor-α and interleukin-6). Multivariable-adjusted stepwise regression was used to develop a metabolite predictor set representative of muscle CSA and the FFMI.
  
  
  RESULTS
  Seven branched chain amino acid-related metabolites were found to be associated with both muscle CSA and the FFMI. Separately, two metabolites were identified as insulin resistance-associated markers of the FFMI, whereas four metabolites were identified as inflammation-associated markers of either muscle CSA or the FFMI. Stepwise models identified combinations of metabolites to explain approximately 68% of the variability inherent in muscle CSA or the FFMI.
  
  
  CONCLUSIONS
  Collectively, we report multiple branched chain amino acids and novel inflammation-associated tryptophan metabolites as markers of muscle CSA or the FFMI in functionally limited older adults.
authors.affiliation: Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, Massachusetts.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lustgarten
authors.affiliation: The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, and Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts.
authors.forename: Lori Lyn
authors.initials: LL
authors.lastname: Price
authors.affiliation: Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, Massachusetts.
authors.forename: Angela
authors.initials: A
authors.lastname: Chale
authors.affiliation: Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, Massachusetts.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Phillips
authors.affiliation: Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, Massachusetts. roger.fielding@tufts.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D001823:Body Composition / Q000502:physiology*; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D055432:Metabolomics / Q000379:methods; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D000597:Amino Acids, Branched-Chain
keywords: Biomarkers; Inflammation; Insulin resistance; Metabolomics.; Muscle